Aneuploidy and RAS mutations are mutually exclusive events in the development of well-differentiated thyroid follicular tumours.

Banito, Ana; Pinto, António E.; Espadinha, Carla; Marques, Ana Rita; Leite, Valeriano

Objective Follicular thyroid tumours present several genetic alterations such as aneuploidy, RAS mutations and PAX8/PPARγrearrangements. The molecular basis of aneuploidy remains undefined in the majority of human cancers. It has been proposed that mutations in RAS oncogenes could be related to chromosomal instability, although this issue remains controversial. The aim of our study was to investigate the correlation between aneuploidy, RAS mutations and PAX8/PPARγ gene rearrangement in thyroid follicular tumours. Design Ploidy status was determined by flow cytometry in 111 thyroid lesions (42 follicular thyroid adenomas, 27 follicular thyroid carcinomas, 19 follicular variants of papillary thyroid carcinoma, 20 poorly differentiated thyroid carcinomas and 3 anaplastic thyroid carcinomas). RAS mutations and PAX8/PPARγ fusion gene were investigated in 101 and 87 of these samples, respectively. Results Altogether, 12 of 50 (24%) diploid tumours presented RAS mutation which contrasts with 3 of 51 (5·9%; P = 0·0124) RAS mutations in the group of aneuploid tumours. The aneuploid tumours harbouring RAS mutations were two poorly differentiated carcinomas and one follicular variant of papillary thyroid carcinoma with poorly differentiated areas. None of the tumours with RAS mutations expressed the PAX8/PPARγ fusion gene. Three of five (60%) follicular thyroid adenomas and 1 of 7 (14%) follicular thyroid carcinomas, with the PAX8/PPARγ fusion gene, were aneuploid. Conclusions Our data suggest that aneuploidy and RAS mutations are mutually exclusive events in the development of well-differentiated thyroid follicular tumours.

THYROID cancer; CANCER genetics; ANEUPLOIDY; PLOIDY; FLOW cytometry; GENETIC mutation; PHYSICAL & theoretical chemistry

Clinical Endocrinology, 2007, Vol 67, Issue 5, p706

0300-0664

Academic Journal

10.1111/j.1365-2265.2007.02949.x